If treatments are actively being titrated up or down, then more frequent serum phosphate checks may be needed

If dialysis adequacy is suboptimal, it may worsen hyperphosphatemia and thus adequacy should be monitored and maximized

Medications, compliance with prescriptions, time of intake of binders in relation to meals, and diet should be reviewed along with lab work

Imaging

If dialysis adequacy is suboptimal, then imaging studies to assess vascular access patency may be needed

Biopsy

If painful non-healing ulcers are discovered and the diagnosis of calciphylaxis is being entertained, a skin biopsy may provide the definitive diagnosis, especially when other skin lesions are also in the differential diagnosis (e.g. Coumadin-induced skin necrosis)

Overall Interpretation of test results

Trends in serum phosphate values are more useful than single measurements

Compliance with three times a day drugs is lower than with once daily medications

Pill burden with certain classes of phosphorus binders is large

Gastrointestinal side effects/lack of palatability may limit compliance

Education about proper intake of medications in relation to food is important

Education about importance of therapy may improve compliance

Largest dose of binder should coincide with largest meal of the day

Administered three times a day with meals

Several classes exist

Aluminum-based phosphate binders

▪ Trap phosphate ions in the blood and form unabsorbable aluminum phosphate precipitates in the gut

▪ Useful for short-term therapy

▪ Toxicities (cognitive, bone, heme) prevent long-term use

Calcium-based phosphate binders

Calcium carbonate

Calcium acetate

Both are effective, inexpensive but use has been curtailed by some due to concerns re hypercalcemia (especially when used in conjunction with active vitamin D) and contribution to vascular calcification (although still controversial and data on hard clinical outcomes lacking)

Recent meta-analyses suggest that calcium carbonate and calcium acetate have similar efficacy in lowering phosphate levels and similar tolerability

Non-calcium based phosphate binders

Sevelamer hydrochloride

▪ Metabolic acidosis

▪ Large pill burden

▪ Cost

Severlamer carbonate

▪ Developed to address concern of metabolic acidosis with sevelamer hydrochloride

Lanthanum carbonate

▪ Potent, less pills needed to accomplish control of serum phosphate

▪ Long-term data on safety available for 9 years of follow-up

▪ Gastrointestinal (GI) side effects limiting (tolerability may be improved when starting a lowest dose and slowly titrating up)

Controversies in patient management

Given concerns for increased risk for vascular calcification with calcium-based binders some have suggested that calcium-based binders should be used sparingly, if at all

The opposing view is that there is insufficient evidence to support the claim that calcium-based binders are harmful. Proponents of this view also cite increased cost associated with non-calcium based binders and thus advocate use of less expensive calcium-based binders.

What happens to patients with hyperphosphatemia?

Natural history and epidemiology and anatomic and/or pathologic consequences

Several epidemiologic studies support increased mortality in those with elevated phosphate levels

Pharmacoepidemiologic studies suggest that use of binders may be protective on dialysis

Physiologic and/or pathophysiologic implications of hyperphosphatemia

Inhibition of 1,25 Vitamin D

Stimulation of FGF23 production

Contribution to the pathogenesis of secondary hyperparathyroidism

Role in vascular calcification development and progression and direct toxicity to other end-organs, including heart and bone

Pharmacologic considerations

Binders need to be taken with meals, with largest dose with biggest meal of day

Dose adjustments and switching to/or adding a different class may be necessary once treated with vitamin D

Pill burden is often an issue

GI side effects are also often limiting

How to utilize team care?

Specialty consultations

If dialysis adequacy is in question, interventional radiologists may need to be consulted to assess patency and perform vascular access procedures as needed

Nurses

enforce medication education, adherence and compliance

Dieticians

Perform dietary assessments and counseling

Educate patients about hidden sources of phosphorus in form of phosphorus-based additives

Multi-disciplinary care teams may be better able to meet target ranges for management

Limitations

Suggested KDOQI range for phosphate (and other mineral metabolites) is difficult to maintain in practice

While an observation study suggested that individuals who are within KDOQI targets have a better survival experience than those who are not, there are insufficient patient-level data to support the target ranges. Both sets of recommendations are limited by insufficient data on hard clinical outcomes.

Dietary recommendations do not take into account hidden sources of phosphorus, or bioavailability of phosphorus in different foods, types of foods (vegetarian vs. not).